13-19935063-A-G

Variant names:

• chr13-19935063-A-G
• rs7320671
• XM_047430584.1:c.-163-15828A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047430584.1(ZMYM2):​c.-163-15828A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,846 control chromosomes in the GnomAD database, including 14,386 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14386 hom., cov: 32)
• Consequence: ZMYM2 XM_047430584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 publications found

Genes affected

ZMYM2 (HGNC:12989): (zinc finger MYM-type containing 2) The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex. Translocation of this gene with the fibroblast growth factor receptor-1 gene (FGFR1) results in a fusion gene, which may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

ZMYM2 Gene-Disease associations (from GenCC):

• neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65724 AN: 151728 Hom.: 14377 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.433 AC: 65749 AN: 151846 Hom.: 14386 Cov.: 32 AF XY: 0.431 AC XY: 31982 AN XY: 74194

African (AFR) AF: 0.506 AC: 20949 AN: 41412

American (AMR) AF: 0.448 AC: 6822 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2060 AN: 5148

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4818

European-Finnish (FIN) AF: 0.425 AC: 4468 AN: 10516

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26836 AN: 67930

Other (OTH) AF: 0.423 AC: 893 AN: 2110

Alfa AF: 0.409 Hom.: 23424

Bravo AF: 0.442

Asia WGS AF: 0.355 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7320671; hg19: chr13-20509203;